Schaftoside ameliorates oxygen glucose deprivation-induced inflammation associated with the TLR4/Myd88/Drp1-related mitochondrial fission in BV2 microglia cells

  • J Pharmacol Sci. 2019 Jan;139(1):15-22. doi: 10.1016/j.jphs.2018.10.012.
Kecheng Zhou  1 ,  Jiayu Wu  1 ,  Jie Chen  1 ,  Ye Zhou  1 ,  Xiaolong Chen  1 ,  Qiaoyun Wu  1 ,  Yangxinzi Xu  2 ,  Wenzhan Tu  1 ,  Xinfa Lou  3 ,  Guanhu Yang  3 ,  Songhe Jiang  4
Affiliations
  • 1. Department of Physical Medicine and Rehabilitation, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; Integrative & Optimized Medicine Research Center, China-USA Institute for Acupuncture and Rehabilitation, Wenzhou Medical University, Wenzhou, Zhejiang, China.
  • 2. Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, Manitoba, Canada.
  • 3. Integrative & Optimized Medicine Research Center, China-USA Institute for Acupuncture and Rehabilitation, Wenzhou Medical University, Wenzhou, Zhejiang, China.
  • 4. Department of Physical Medicine and Rehabilitation, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; Integrative & Optimized Medicine Research Center, China-USA Institute for Acupuncture and Rehabilitation, Wenzhou Medical University, Wenzhou, Zhejiang, China. Electronic address: [email protected].
PMID: 30528467 DOI: 10.1016/j.jphs.2018.10.012
Abstract

Background: Neuroinflammation plays a major role in the development of ischemic stroke, and regulation of the proinflammatory TLR4 signaling pathway in microglia stands to be a promising therapeutic strategy for stroke intervention. Recently, the homeostasis of mitochondrial dynamics has also been raised as a vital component in maintaining neuronal health, but its relevance in microglia hasn't been investigated. Schaftoside, a natural flavonoid compound and a promising treatment for inflammation, has demonstrated potency against LPS-induced lung inflammation in mice; however, its action on TLR4-induced neuroinflammation and mitochondrial dynamics in microglia is still unknown.

Methods: The effects of schaftoside in regulating inflammation and mitochondrial dynamics were investigated in vitro in oxygen glucose deprivation (OGD)-stimulated BV2 microglia cells.

Results: Schaftoside inhibited mRNA and protein expressions of proinflammatory cytokines (IL-1β, TNF-α, and IL-6) after 4 h in OGD-stimulated BV2 microglia cells, similar to the effect of TAK242, an inhibitor of TLR4. TLR4/MyD88 signaling pathway was effectively suppressed by schaftoside. In addition, both schaftoside and TAK242 treatments significantly decreased Drp1 expression, phosphorylation, translocation and mitochondrial fission in OGD-stimulated BV2 cells.

Conclusions: Our study suggested that schaftoside was able to reduce neuroinflammation, which is mediated in part by reducing TLR4/MyD88/Drp1-related mitochondrial fission in BV2 microglia cells.

Keywords
Microglia; Mitochondrial fission; Schaftoside; Stroke; TLR4.
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